68 research outputs found
Formacion de medicos y paramedicos en Chile. Antecedentes, problemas y perspectivas
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Photodegradation of nimodipine and felodipine in microheterogeneous systems
Get PDFIndexación: Web of Science; ScieloThe photochemical behavior of nimodipine (NIMO) and felodipine (FELO), photolabile drugs widely used as antihypertensive calcium channel blockers, is studied in constrained media. Specifically, we are interested in the kinetic analysis of 4-aryl-1,4-dihydropyridine photodegradation processes when they are incorporated in biological-mimicking systems like micelles or liposomes. In order to establish if the nature of the head of surfactant (ionic or nonionic) could be important modulating the photo-reactivity of these drugs, we studied the photodegradation of NIMO and FELO incorporated in micelles formed with sodium dodecyl sulfate (SDS, anionic), dodecyl-pyridinium chloride (DPC, cationic) and mono lauryl sucrose ester (MLS, nonionic) as surfactants. Additionally, the results of the photodegradation of these compounds in liposomes were also included. The results clearly indicate that both dihydropyridines studied, NIMO and FELO, are located near to the interface, but the surface charge of micelles does not affect neither, the photodegradation rate constant nor the photodegradation products profile. The absence of singlet oxygen generation in micellar media is consistent with the proposition of these 4-aryl-1,4-dihidropyridines located near to the interface of the micelle, where a polar environment is sensed. In addition, the ethanol preferential location on membranes and dihydropyridine enhanced photodegradation by alcohol presence are interesting results to consider in future research.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072012000300025&nrm=is
Parametrización de moléculas orgánicas y análisis de su interacción con dendrímeros de PAMAM de distintas generaciones mediante técnicas de química cuántica y dinámica molecular
Get PDF115 p.Los dendrímeros son nanoparticulas con propiedades características, tales como tamaño a nanoescala, forma globular, un número bien definido de grupos funcionales en la superficie y baja polidispersidad. Dentro de estos los más estudiados son los dendrímeros PAMAM que poseen cavidades internas vacías y muchos grupos amino terminales responsables de una alta solubilidad y reactividad. PAMAM posee un alto potencial para lograr mejorar la solubilidad de fármacos ampliamente utilizados en diferentes tratamientos médicos. Un Estudio experimental llevado a cabo por Cheng y col. (2008), en el que
fármacos de pobre solubilidad (Fenobarbital y Primidona) se mezclaron con PAMAM de distintas generaciones, llegó a la conclusión que el Fenobarbital mejoraba su solubilidad, a diferencia de lo que pasaba con la Primidona y que las energías de interacción predominantes entre los dendrímeros PAMAM con el Fenobarbital fueron las electrostáticas.
Basándose en los estudios experimentales anteriormente descritos, el objetivo
de este trabajo es estudiar y caracterizar las interacciones entre los fármacos
Primidona y Fenobarbital con dendrímeros tipo PAMAM de diversas generaciones usando metódos de Docking Molecular, Química Cuántica y Dinámica Molecular. Para lograr este objetivo la metodología se dividió en dos etapas. En la primera se realizaron cálculos de Docking Molecular y Química cuántica sobre los 16
posibles complejos formados por PAMAM G0-NH2, PAMAM G0-NH3, PAMAM G1-NH2 y PAMAM G1-NH3, y los medicamentos Fenobarbital y Primidona en sus estados cargado y neutro. En la segunda etapa se efectuaron cálculos de Docking Molecular y Dinámica Molecular utilizando el dendrímero PAMAM G4-NH3 con los fármacos
Fenobarbital y Primidona en sus estados cargado y neutro. Una vez finalizados los
cálculos se llevó a cabo el ánalisis de la interacción entre los fármacos y los
dendrímeros PAMAM.Los resultados Químico Cuánticos mostraron que las mejores interacciones ocurren entre los PAMAM y los fármacos Fenobarbital y Primidona negativamente cargados en comparación a los mismos fármacos en estado neutro, debido
posiblemente a que sus cargas pueden realizar interacciones electrostáticas con
mayor facilidad. Los resultados de las Dinámicas Moleculares muestran lo mismo,
aunque cabe destacar que la interacción de PAMAM con Fenobarbital neutro es bastante estable, a diferencia de lo que ocurre con la Primidona neutra, que no realiza
mayor interacción con el endrímero./ABSTRACT:
Dendrimers are nanoparticles with featured properties, such as nano-scaled,
globular shapes, well-defined number of peripheral functional groups and low
polydispersity. Within these, the most studied are PAMAM dendrimers which have
empty internal cavities and many terminal amino groups, which are responsible for
high solubility and reactivity. PAMAM have high potencial for improving the solubility
of drugs widely used in different medical therapies.An experimental study was carried out by Cheng y col. (2008) in which poorly
soluble drugs (Phenobarbital y Primidone) interacting with PAMAM dendrimers. The
results showed that PAMAM dendrimers significantly increased the solubilities of
phenobarbital and the solubility of primidone was scarcely changed. In addition,
concluded that the the electrostatic interaction contributes more to the solubility enhancement of phenobarbital than encapsulation. Based on the experimental studies described above, the objective of this work is to study and describe interactions between Phenobarbital and Primidone with PAMAM dendrimers using using methods of Quantum Chemistry, Molecular Ddocking and Molecular Dynamics.
To achieve this goal the methodology is divided into two phases. In the first
Molecular Docking and Quantum Chemistry calculations were performed for all
possible complexes formed by PAMAM G0-NH2, G0-NH3, G1-NH2, G1-NH3 y G4-NH3
and Phenobarbital and Primidone drugs in their charged and neutral state. In the
second phase Molecular Docking and Molecular Dynamics calculations were performed using PAMAM G4-NH3 and Phenobarbital and Primidone drugs in their charged and neutral state. After completion of calculation, analysis of interaction between drugs and PAMAM dendrimers was performed. Quantum Chemistry results showed that the best interactions occurs between PAMAM and Phenobarbital and Primidone in their charged state compared to the same drugs in neutral state, due to charges electrostatic interactions can be
performed more easily. Molecular Dynamics results showed the same, although it
should be noted that the interaction between PAMAM and Phenobarbital in neutral
state is quite stable, in contrast to what happens with Primidone in neutral state, which does not interact with dendrimer
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